Critical Review of Biodegradable and Bioactive Polymer Composites for Bone Tissue Engineering and Drug Delivery Applications

Abstract

In the determination of the bioavailability of drugs administered orally, the drugs' solubility and permeability play a crucial role. For absorption of drug molecules and production of a pharmacological response, solubility is an important parameter that defines the concentration of the drug in systemic circulation. It is a challenging task to improve the oral bioavailability of drugs that have poor water solubility. Most drug molecules are either poorly soluble or insoluble in aqueous environments. Polymer nanocomposites are combinations of two or more different materials that possess unique characteristics and are fused together with sufficient energy in such a manner that the resultant material will have the best properties of both materials. These polymeric materials (biodegradable and other naturally bioactive polymers) are comprised of nanosized particles in a composition of other materials. A systematic search was carried out on Web of Science and SCOPUS using different keywords, and 485 records were found. After the screening and eligibility process, 88 journal articles were found to be eligible, and hence selected to be reviewed and analyzed. Biocompatible and biodegradable materials have emerged in the manufacture of therapeutic and pharmacologic devices, such as impermanent implantation and 3D scaffolds for tissue regeneration and biomedical applications. Substantial effort has been made in the usage of bio-based polymers for potential pharmacologic and biomedical purposes, including targeted deliveries and drug carriers for regulated drug release. These implementations necessitate unique physicochemical and pharmacokinetic, microbiological, metabolic, and degradation characteristics of the materials in order to provide prolific therapeutic treatments. As a result, a broadly diverse spectrum of natural or artificially synthesized polymers capable of enzymatic hydrolysis, hydrolyzing, or enzyme decomposition are being explored for biomedical purposes. This summary examines the contemporary status of biodegradable naturally and synthetically derived polymers for biomedical fields, such as tissue engineering, regenerative medicine, bioengineering, targeted drug discovery and delivery, implantation, and wound repair and healing. This review presents an insight into a number of the commonly used tissue engineering applications, including drug delivery carrier systems, demonstrated in the recent findings. Due to the inherent remarkable properties of biodegradable and bioactive polymers, such as their antimicrobial, antitumor, anti-inflammatory, and anticancer activities, certain materials have gained significant interest in recent years. These systems are also actively being researched to improve therapeutic activity and mitigate adverse consequences. In this article, we also present the main drug delivery systems reported in the literature and the main methods available to impregnate the polymeric scaffolds with drugs, their properties, and their respective benefits for tissue engineering.

Keywords: anticancer activity; antimicrobial properties; biodegradable polymers; drug delivery; natural bioactive polymers; polymeric scaffolds; tissue engineering.

Figure 1

Infographic word-cloud visualization of the semantic clustering network of the keywords for physicomechanical, thermostability, and in vitro drug release studies of bioactive/biodegradable polymeric materials with remarkable biocompatibility in biomedical research.

Figure 2

Microstructure of mineralized PLLA matrices: (a) electro-deposition at 3 V, 60 °C for 1 h; (b) high-magnification picture of (a,c) mineralized in 1.5 SBF for 12 days; (d) magnified image of (c,e) mineralized in 1.5 SBF for one month; and (f) magnified picture of (e). Reproduced with permission from [33].

Figure 3

Cell viability of chitosan (CS) nanocomposite hydrogel nanoparticles (CNPs). Reproduced with permission from [34].

Figure 4

Diclofenac-embedded pure CS-NPs, CNPs1, and CNPs2 in vitro release of drugs studied at 37 °C in varying acid levels and environmental conditions: (a) pH 2, (b) pH 6, (c) pH 7.4, and (d) pH 9. The results are presented as an average deviation of ±3. Reproduced with permission from [34].

Figure 5

Physicomechanical analysis of biopolymer composite films employing quantitative techniques: (a) load displacement; (b) ultimate strength elastic moduli; and (c) impact–strength–strain graphs from uni-axial tensile nanocomposite thin films. (d) SEM micrographs of the fractography of biopolymeric nanocomposites comprising 5% of f-CNOs, produced by tear testing on perforated grooved specimens. Reproduced with permission from [35].

Figure 6

Systematic mapping summary of scientific advances in physicomechanics and thermostability in in vitro drug release studies of biopolymeric materials/biocomposites for biomedical applications.

Figure 7

(a) Tensile graphs; (b–e) contact angles of neat PCL, PD, PDC (0.5 wt.%), and PDC (1.0 wt.%); and (f,g) porosity/permeability of PDC (0.5 wt.%) and PDC (1.0 wt.%) composite filaments. Reproduced with permission from [297].

Figure 8

(a) Tensile strength; (b) degradation; (c) water contact angle for virgin BSA, BSA/f-CNOs-1, and BSA/f-CNOs-2 filaments; (d) porosity/permeability of biomimetic or biocompatible BSA/f-CNOs-2 nanocomposite fibrils. Reproduced with permission from [298].

Figure 9

Graphs demonstrating hydrogel physicomechanical characteristics: (a) tensile stress; (b) tensile strain versus elastic moduli; (c) impact strength; and (d) storage and loss modulus (G′ G″). Reproduced with permission from [301].

Figure 10

(i) Tensile strength; (ii) tensile moduli; (iii) fracture strain; (IV) moduli of rupture/bending strength; (V) bending modulus of unprocessed and 5N-72-treated coir-fiber/PBS biodegradable composites; and tensile fracturing surfaces of PBS biodegradable composite strengthened with 20% weight concentration of: (a) unprocessed coir fibers, (b) 5N-72 processed coir-fibers. Reproduced with permission from [303].

Figure 11

Microstructure of layered 2 (a–c) and Lam 1:6 (d–f) under numerous varied magnification scales. Reproduced with permission from [304].

Figure 12

Loading versus displacement graphs from: (a) tensile test; (b) compression test; and (c) bending test. Reproduced with permission from [305].

Figure 13

A graphical description highlighting the numerous promising functionalities of biodegradable polymerics with numerous filler particles. Reproduced with permission from [313].

Figure 14

Visualization summarizing the numerous potentially attractive characteristics of biodegradable/bioactive polymerics for biomedical applications.

Figure 15

Number of articles published per year.

Figure 16

(a) Number of relevant articles (n = 88) by journal. (b) Number of relevant journal articles (n = 88) by publisher.

Figure 17

(a) Number of papers published (n = 88) according to the author’s institute. (b) Number of papers published (n = 88) according to the author’s institute and field of study.

Figure 17

(a) Number of papers published (n = 88) according to the author’s institute. (b) Number of papers published (n = 88) according to the author’s institute and field of study.

Figure 18

Number of papers published (n = 88) according to the geographical location and country affiliation.

Figure 19

Number of papers published (n = 88) according to the most active authors.

Figure 20

The method in which the scaffold is immersed in the drug solution. Reproduced with permission from [1].

Figure 21

The formation of the system during fabrication. Reproduced with permission from [1].

Figure 22

The 3D printing method. Reproduced with permission from [1].

Figure 23

Layer-by-layer method. Reproduced with permission from [1].

Figure 24

Bibliometric analysis of the utilization of biodegradable and other natural polymeric biomaterials in hard tissue engineering applications.

Figure 25

Schematic flow diagram indicating that hierarchical bone arrangement relies on the self-assembly of triple helices of collagen and the accumulation on the surface by HAp-precipitated crystals. The formation of structured and layered fibrous assemblies and osteons (i.e., concentric strands) corresponds to later measures. Reproduced with permission from [319].

Figure 26

Influence of concentration on the cumulative percentage of drug delivery at (a) 0.05%, (b) 0.1%, and (c) 0.15% of capoten-loaded nanocomposite hydrogels. Reproduced with permission from [322].

Figure 27

Comparison of in vitro dissolution characteristics of Meloxicam/Poloxamer solid dispersions fabricated using (a) the melting process and (b) the microwave method. Reproduced with permission from [327].

Figure 28

DSC thermogram. Solid line: Composite BI1; the 75 °C peak conforms to the melting point of the microcrystalline ibuprofen stage, whereas the β-CD dehydration is correlated with the highest point at 85 °C. Broken/dotted line: Composite PN1; the maximum point is correlated with the melting of the microcrystalline nimesulide stage. Reproduced with permission from [330].

Figure 29

Quantity of (a) chitosan/miconazole nitrate and (b) chitosan/clotrimazole microspheres released in vitro from the drug at diverse pressures at various concentrations. Reproduced with permission from [332].

Figure 30

(a,b) In vitro drug release of synthesized hydrophilic polymer–gel in various formulations; (c) in vitro drug release of synthesized hydrophilic polymer–gel in the marketed product formulation; and (d,e) ex vivo drug release profile of developed gels in different formulations. Reproduced with permission from [333].

Figure 31

(a) Comparison of the solubility between the physical KEAC combination and KENC. (b) Correlations of solubility in KEGG physical blend and KEGG bio-nanocomposite. The information is the average ± SD, n = 3. The results are expressed in terms of the solubility percentage of virgin ketoprofen, where: KE–ketoprofen, AC–acacia, GG–ghatti gum, SD–standard deviation. Reproduced with permission from [335].

Figure 32

Schematic representing the bursting effect in a zero-ordered drug delivery system. Reproduced with permission from [336].

Figure 33

Bibliometric analysis of the utilization of natural polymeric biomaterials and nanopolymers in drug carriers and tissue engineering applications.

Figure 34

Bibliometric mapping of the antimicrobial drug delivery of biodegradable and natural polymeric biomaterials in hard tissue engineering.

Figure 35

Antitumor drug delivery of biodegradable and natural polymeric biomaterials in hard tissue engineering.

Figure 36

Drug delivery system for bone cancer.

Figure 37

Scientometric bio-informatic mapping of anti-inflammatory drug delivery of biodegradable and natural polymeric biomaterials in hard tissue engineering.